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Background: Burr hole evacuation is a well-established treatment for symptomatic cases with chronic subdural hematoma (cSDH). Routinely postoperative catheter is left in the subdural space to drain the residual blood. Drainage obstruction is commonly seen, and it can be related to suboptimal treatment. Methods: Two groups of patients submitted to cSDH surgery were evaluated in a retrospective non-randomized trial, one group that had conventional subdural drainage (CD group, n ​= ​20) and another group that used an anti-thrombotic catheter (AT group, n ​= ​14). We compared the obstruction rate, amount of drainage and complications. Statistical analyses were done using SPSS (v.28.0). Results: For AT and CD groups respectively (median ​± ​IQR), the age was 68.23 ​± ​26.0 and 70.94 ​± ​21.5 (p ​> ​0.05); preoperative hematoma width was 18.3 ​± ​11.0 ​mm and 20.7 ​± ​11.7 ​mm and midline shift was 13.0 ​± ​9.2 and 5.2 ​± ​8.0 ​mm (p ​= ​0.49). Postoperative hematoma width was 12.7 ​± ​9.2 ​mm and 10.8 ​± ​9.0 ​mm (p ​

Background: Stiff person syndrome spectrum disorders (SPSD) are a rare group of disabling neuroimmunological disorders. SPSD often requires immune therapies, especially in the setting of inadequate response to symptomatic treatments. The safety and efficacy of therapeutic plasma exchange (TPE) in SPSD remains uncertain. Objectives: To describe the safety, tolerability, and efficacy of TPE in patients with SPSD. Design: A retrospective observational study. Methods: A retrospective review of SPSD patients seen at Johns Hopkins Hospital (JHH) from 1997 to 2021 was performed. Patient demographics/history, examination/diagnostic findings, treatment response, and TPE-related complications were recorded. Assessment for any associations between clinical characteristics, including age, sex, clinical phenotype, and time on immunotherapy, and response to TPE 3 months after treatment was performed. A subgroup of 18 patients treated with TPE at JHH and 6 patients treated with TPE at outside institutions were evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment. Literature review of SPSD and TPE was also conducted. Results: Thirty-nine SPSD patients were treated with TPE (21 at JHH and 18 at outside institutions); median age 48 years, 77% female, median modified Rankin Scale 3; mean initial anti-GAD65 antibody titer was 23,508 U/mL. Twenty-four patients (62%) had classic SPS, 10 (26%) had SPS-plus, 2 (5%) had progressive encephalomyelitis with rigidity and myoclonus, and 3 (8%) had pure cerebellar ataxia. All patients were on symptomatic treatments, 30 (77%) previously received IVIg, and 3 (8%) previously received rituximab. Four patients (10%) had a TPE-related adverse event. One developed asymptomatic hypotension, another had both line thrombosis and infection, and two had non-life-threatening bleeding events. Twenty-three (59%) patients reported improvement in symptoms after TPE. Of the subgroup of 24 patients evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment, 14 (58%) required fewer GABAergic symptomatic medications. Literature review identified 57 additional patients with SPSD; 43 (75%) reported temporary improvement after TPE. Conclusion: The majority of patients treated with TPE had improvement. Moreover, most patients evaluated for any change in usage of symptomatic medications after the TPE treatment no longer required as much symptomatic medications months after TPE. TPE appears safe and well-tolerated in SPSD. Further studies are needed to assess the long-term efficacy of TPE in SPSD and identify which patients may benefit the most from TPE.

Abstract Forage fishes are a critical food web link in marine ecosystems, aggregating in a hierarchical patch structure over multiple spatial and temporal scales. Surface‐level forage fish aggregations (FFAs) represent a concentrated source of prey available to surface‐ and shallow‐foraging marine predators. Existing survey and analysis methods are often imperfect for studying forage fishes at scales appropriate to foraging predators, making it difficult to quantify predator–prey interactions. In many cases, general distributions of forage fish species are known; however, these may not represent surface‐level prey availability to predators. Likewise, we lack an understanding of the oceanographic drivers of spatial patterns of prey aggregation and availability or forage fish community patterns. Specifically, we applied Bayesian joint species distribution models to bottom trawl survey data to assess species‐ and community‐level forage fish distribution patterns across the US Northeast Continental Shelf (NES) ecosystem. Aerial digital surveys gathered data on surface FFAs at two project sites within the NES, which we used in a spatially explicit hierarchical Bayesian model to estimate the abundance and size of surface FFAs. We used these models to examine the oceanographic drivers of forage fish distributions and aggregations. Our results suggest that, in the NES, regions of high community species richness are spatially consistent with regions of high surface FFA abundance. Bathymetric depth drove both patterns, while subsurface features, such as mixed layer depth, primarily influenced aggregation behavior and surface features, such as sea surface temperature, sub‐mesoscale eddies, and fronts influenced forage fish diversity. In combination, these models help quantify the availability of forage fishes to marine predators and represent a novel application of spatial models to aerial digital survey data.

Summary: Background: Firearm injury (FI) is the leading cause of death in children and adolescents in the United States (US). We describe the epidemiology of pediatric FI-associated emergency department (ED) visits and hospitalizations in the US stratified by race and ethnicity. Methods: Data on pediatric (0–17-year-olds) FI were analyzed using the 2019 Nationwide Emergency Department Sample (NEDS) and Kids’ Inpatient Database (KID), the largest all-payer databases in the US for ED visits and pediatric hospitalizations, respectively. FI encounters were stratified by race and ethnicity. Poisson regression was used to identify factors associated with in-hospital mortality. Sampling weights were applied to generate nationally representative estimates. Findings: There were 7017 pediatric ED visits with FI (NEDS); 85.0% (5961/7017) were male and 73.0% (5125/7017) were adolescents (15–17 years). Overall, 5.5% (384/7017) died in the ED; 53.1% (3727/7017) of ED encounters did not result in hospitalization. There were 2817 pediatric FI hospitalizations (KID); 84.1% (2369/2817) were male and 71.6% (2018/2817) were adolescents; 51.4% (1447/2817) of FI were unintentional, 42.8% (1207/2817) were assault-related, and 5.8% (163/2817) were self-inflicted. Black children had the highest proportion (52.6%; 1481/2817) of hospitalizations among all race and ethnicities (p

Objective: Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately.Approach: Patient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants. Missense/in-frame variants were further classified as transmembrane or non-transmembrane based on whether they affected amino acid residues predicted to be in transmembrane domains of WFS1. Statistical analysis was performed using Wilcoxon rank-sum tests with multiple test adjustment applied via the Bonferonni correction.Results: A greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by diabetes mellitus and optic atrophy emerging significantly earlier in patients with two nonsense/frameshift variants compared with zero or one nonsense/frameshift variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy among patients with either one or two in-frame variants.Summary/Conclusion: The results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.

Background: Cutibacterium acnes is a common pathogen leading to postoperative shoulder infections. Many centers are utilizing 5% topical benzoyl peroxide (BPO) gel to decrease cutibacterium acnes bioburden prior to surgery. The purpose of this study was to evaluate patient compliance, tolerance, and side effects of applying BPO to the shoulder prior to surgery. Our hypothesis was that BPO would be well tolerated with few, minor side effects, and patients would comply with a regimen of 5 treatments spanning 48 hours prior to surgery. Methods: All patients undergoing operative intervention, either open or arthroscopic, about the shoulder from August 7, 2020, through July 15, 2021, by a single surgeon were instructed to apply BPO to the shoulder after showering, on dry skin, in the morning and evening, starting 48 hours before their surgical date. Patients were instructed to apply a half-dollar-sized quantity for each treatment. There were a total of 5 topical applications. On the day of surgery, patients were given a 6-question survey regarding side effects experienced, BPO treatments missed, ease of treatment, and a scenario question. Demographic information was collected, and a satisfaction survey was administered upon study completion. Results: A total of 183 patients out of a possible 284 eligible patients (64.4%) completed the survey. The median (interquartile range) age at surgery was 59.9 years. Sixty-four participants (35%) in the study cohort were female. One-hundred thirteen (61.7%) had an arthroscopic surgical approach, whereas 70 (38.3%) underwent open shoulder surgery. Most patients (N = 152, 83.5%) experienced no side effects from the topical 5% BPO gel treatments. Twenty-two (12.0%) patients missed 1 treatment, 10 (5.5%) missed 2 treatments, 1 (0.5%) missed 3 treatments, 3 (1.6%) missed 4 treatments, and 4 (2.2%) missed all 5 treatments. The majority of patients, 143 (78.1%), completed all 5 treatments. When prompted to choose between serial skin preparation treatments at home leading up to surgery or a single light-based decolonization procedure in the preoperative holding area on the day of surgery, 111 (60.7%) preferred to undergo antimicrobial treatment at home and arrive for surgery as otherwise scheduled. Conclusion: Serial preoperative applications of topical 5% BPO gel are well tolerated by the majority of patients. Over 20% of patients missed at least one application of BPO. Most patients prefer home-based antimicrobial treatments compared with arriving earlier on the day of surgery for a single light-based antimicrobial treatment.

Abstract Introduction Engagement in physical activity (PA) is a critical component of behavioral weight loss (BWL) treatment. Subjective experiences surrounding PA may shape exercise decisions and need to be further understood within a BWL sample. Methods Participants in this study were adults with overweight/obesity enrolled in an 18‐month BWL program. At baseline, six, and 18 months, participants (N = 320) predicted how they would feel during a lab‐based walking task and rated their experiences mid‐walk and post‐walk. They also completed self‐report questionnaires assessing depressive symptoms and discomfort intolerance. Results and Discussion Results indicated that exercise experience and expectations were more positive at later treatment points than at baseline. At each assessment point, post‐walk ratings were more positive than mid‐walk ratings, but pre‐walk ratings did not differ from mid‐walk ratings, suggesting BWL participants were relatively accurate in predicting their PA experience. These results suggest treatment‐seeking adults with overweight/obesity feel most positive upon completion of PA, may not experience a forecasting bias as hypothesized and seem to have increasingly positive PA expectations and experiences as they proceed through treatment and lose weight. Lower discomfort intolerance and depressive symptoms were associated with more positive PA expectations and experiences. Understanding these individual differences in PA experience can inform intervention strategies.

The laboratory measurements conducted on Vaca Muerta formation samples demonstrate stress-dependent elastic behavior and compaction under representative in situ conditions. The experimental results reveal that the analyzed samples display elastoplastic deformation and shear-enhanced compaction as primary plasticity mechanisms. These experimental findings contradict the expected linear elastic response anticipated before brittle failure, as reported in several studies on the geomechanical characterization of the Vaca Muerta formation. Therefore, we present a comprehensive laboratory analysis of Vaca Muerta formation samples showing their nonlinear elastic behavior and irrecoverable shear-enhanced compaction. Additionally, we calibrate an elastoplastic constitutive model based on these experimental observations. The resulting model accurately reproduces the observed phenomena, playing a pivotal role in geoengineering applications within the energy industry.

Vaccines continue to play an enormous role in the progression of aquaculture industries worldwide. Though preventable diseases cause massive economic losses, injection-based vaccine delivery is cost-prohibitive or otherwise impractical for many producers. Most oral vaccines, which are much cheaper to administer, do not provide adequate protection relative to traditional injection or even immersion formulas. Research has focused on determining why there appears to be a lack of protection afforded by oral vaccines. Here, we review the basic immunological principles associated with oral vaccination before discussing the recent progress and current status of oral vaccine research. This knowledge is critical for the development and advancement of efficacious oral vaccines for the aquaculture industry.

Abstract Background Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8). Methods MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated. Discussion Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda. Trial registration Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669 . Registered on 9 November 2018

Ephrin-B1,-B2 and -B3 proteins share a high degree of sequence similarity. Investigation of these proteins as putative prognostic markers in human cancers including oral squamous cell carcinoma (OSCC) has been limited by challenges in generating specific antibodies against them. The current study examined the reactivity of a polyclonal anti-human ephrin-B2 antibody (HPA008999) against ephrin-B proteins and investigated the prognostic significance of immunoreactivity of the same antibody at different intra-tumor sites in OSCC specimens. By amino acid sequence comparison, immunocytochemistry and Western blot analysis on cell lysates and precipitates from HEK-293T cells transfected with EFNB1, EFNB2, or EFNB3 expression constructs, we demonstrated that HPA008999 reacted to all ephrin-B proteins. Using immunohistochemistry (IHC) with the HPA008999 antibody in a cohort (n = 131) of OSCC, we showed high immunoreactivity at the tumor center, but not at the tumor invading front, was significantly associated with worse 5-year overall survival probabilities. In conclusion, the HPA008999 antibody reacted to all ephrin-B proteins and the immunoreactivity at the tumor center might be useful as a prognostic marker in OSCC. These data underscore the need for the investigation of antibodies for cross-reactivity to similar protein members for obtaining reliable and meaningful results in IHC based biomarker studies.

Abstract Background Adults with behavioral health disorders in criminal-legal systems are at heightened risk of suicide relative to the general population. Despite documented racial disparities in criminal processing and behavioral health treatment, few studies have examined racial differences in suicide risk in this already high-risk population. This study examined 1) the correlates of suicide risk in this population overall and by race and 2) the moderating role of race in these associations. Methods We investigated correlates of clinician-rated suicide risk at baseline in a statewide sample of 2,827 Black and 14,022 White adults with criminal-legal involvement who engaged in community-based behavioral health treatment. Regression-based approaches were used to model suicide risk and test for evidence of interaction effects. Results Findings showed the strongest correlates of suicide risk were greater behavioral health needs, evidence of self-harm, and a primary mental health diagnosis or co-occurring diagnosis. In race-specific analyses, correlates of suicide risk were mostly similar for both Black and White clients, with a couple exceptions. Interaction terms testing between-group effects on correlates of suicide risk were non-significant. Conclusions Adults with behavioral health disorders in criminal-legal systems experience similar risk factors for suicide as the general population. Similar to prior research, we found that Black adults, in particular, are at lower risk for suicide overall. Contrary to expectations, we found similarities in correlates of suicide risk across race in our sample of felony-level adults with behavioral health disorders in the criminal-legal system. Prior research shows that behavioral health professionals should be cognizant of cultural factors when developing a comprehensive approach to suicide care and treatment. Our findings show correlates of suicide risk are largely stable in Black and White adults involved in criminal-legal systems, suggesting culturally responsive treatment for suicide risk should target shared risk factors.

Summary: During childhood, neural systems supporting high-level cognitive processes undergo periods of rapid growth and refinement, which rely on the successful coordination of activation across the brain. Some coordination occurs via cortical hubs—brain regions that coactivate with functional networks other than their own. Adult cortical hubs map into three distinct profiles, but less is known about hub categories during development, when critical improvement in cognition occurs. We identify four distinct hub categories in a large youth sample (n = 567, ages 8.5–17.2), each exhibiting more diverse connectivity profiles than adults. Youth hubs integrating control-sensory processing split into two distinct categories (visual control and auditory/motor control), whereas adult hubs unite under one. This split suggests a need for segregating sensory stimuli while functional networks are experiencing rapid development. Functional coactivation strength for youth control-processing hubs are associated with task performance, suggesting a specialized role in routing sensory information to and from the brain’s control system.

Functional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion and differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) images makes their alignment a challenge. Typically, field map data are used to correct EPI distortions. Alignments achieved with field maps can vary greatly and depends on the quality of field map data. However, many public datasets lack field map data entirely. Additionally, reliable field map data is often difficult to acquire in high-motion pediatric or developmental cohorts. To address this, we developed Synth, a software package for distortion correction and cross-modal image registration that does not require field map data. Synth combines information from T1w and T2w anatomical images to construct an idealized undistorted synthetic image with similar contrast properties to EPI data. This synthetic image acts as an effective reference for individual-specific distortion correction. Using pediatric (ABCD: Adolescent Brain Cognitive Development) and adult (MSC: Midnight Scan Club; HCP: Human Connectome Project) data, we demonstrate that Synth performs comparably to field map distortion correction approaches, and often outperforms them. Field map-less distortion correction with Synth allows accurate and precise registration of fMRI data with missing or corrupted field map information.

Abstract Background While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. Methods We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. Results To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. Conclusions Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.

Babesia spp. are tickborne parasites that cause the clinical infection babesiosis, which has an increasing incidence in the United States. We performed an analysis of hospitalizations in the United States during 2010–2016 in which babesiosis was listed as a diagnosis. We used the National Inpatient Sample database to characterize the epidemiology of Babesia–associated admissions, reflecting severe Babesia-related disease. Over a 7-year period, a total of 7,818 hospitalizations listed babesiosis as a primary or secondary admitting diagnosis. Hospitalizations were seasonal (71.2% occurred during June–August) and situated overwhelmingly in the Northeast and Midwest. The patients were predominantly male and of advanced age, which is consistent with the expected epidemiology. Despite a higher severity of illness in more than (58.5%), the mortality rate was low (1.6%). Comparison with state reporting data suggests that the number of hospitalized persons with babesiosis increased modestly during the observation period.

Abstract There has been growing interest in using wearable physiological monitors to passively detect the signals of distress (i.e., increases in autonomic arousal measured through increased electrodermal activity [EDA]) that may be imminently associated with suicidal thoughts. Before using these monitors in advanced applications such as creating suicide risk detection algorithms or just-in-time interventions, several preliminary questions must be answered. Specifically, we lack information about whether: (1) EDA concurrently and prospectively predicts suicidal thinking and (2) data on EDA adds to the ability to predict the presence and severity of suicidal thinking over and above self-reports of emotional distress. Participants were suicidal psychiatric inpatients (n = 25, 56% female, M age = 33.48 years) who completed six daily assessments of negative affect and suicidal thinking duration of their psychiatric inpatient stay and 28 days post-discharge, and wore on their wrist a physiological monitor (Empatica Embrace) that passively detects autonomic activity. We found that physiological data alone both concurrently and prospectively predicted periods of suicidal thinking, but models with physiological data alone had the poorest fit. Adding physiological data to self-report models improved fit when the outcome variable was severity of suicidal thinking, but worsened model fit when the outcome was presence of suicidal thinking. When predicting severity of suicidal thinking, physiological data improved model fit more for models with non-overlapping self-report data (i.e., low arousal negative affect) than for overlapping self-report data (i.e., high arousal negative affect). These findings suggest that physiological data, under certain contexts (e.g., when combined with self-report data), may be useful in better predicting—and ultimately, preventing—acute increases in suicide risk. However, some cautious optimism is warranted since physiological data do not always improve our ability to predict suicidal thinking.

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease, besides Alzheimer’s Disease, characterized by multiple symptoms, including the well-known motor dysfunctions. It is well-established that there are differences in the fecal microbiota composition between Parkinson’s disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park 25 ) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park 25 flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park 25 flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park 25 flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.

Betaine-homocysteine methyltransferase (BHMT) catalyzes the transfer of methyl groups from betaine to homocysteine (Hcy), producing methionine and dimethylglycine. In this work, we characterize Bhmt wild type (Bhmt-WT) and knockout (Bhmt-KO) mice that were fully backcrossed to a C57Bl6/J background. Consistent with our previous findings, Bhmt-KO mice had decreased body weight, fat mass, and adipose tissue weight compared to WT. Histological analyses and gene expression profiling indicate that adipose browning was activated in KO mice and contributed to the adipose atrophy observed. BHMT is not expressed in adipose tissue but is abundant in liver; thus, a signal must originate from the liver that modulates adipose tissue. We found that, in Bhmt-KO mice, homocysteine-induced endoplasmic reticulum (ER) stress is associated with activation of the hepatic transcription factor cyclic AMP response element binding protein (CREBH), and an increase in hepatic and plasma concentrations of fibroblast growth factor 21 (FGF21), which is known to induce adipose browning. Our data indicate that the deletion of a single gene in one-carbon metabolism modifies adipose biology and energy metabolism. Future studies could focus on identifying if functional polymorphisms in BHMT result in a similar adipose atrophy phenotype.

IntroductionResting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings.MethodsIn this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional MRI data acquired in n = 2010 healthy participants. After training, maps that represent the probability of a voxel belonging to a particular RSN were generated for each participant, and then used to calculate mean and standard deviation (STD) probability maps, which are made publicly available. Further, we compared our results to previously published resting state and task-based functional mappings.ResultsOur results indicate this method can be applied in individual subjects and is highly resistant to both noisy data and fewer RS-fMRI time points than are typically acquired. Further, our results show core regions within each network that exhibit high average probability and low STD.DiscussionThe 3DCNN algorithm can generate individual RSN localization maps, which are necessary for clinical applications. The similarity between 3DCNN mapping results and task-based fMRI responses supports the association of specific functional tasks with RSNs.

IntroductionCassava (Manihot esculenta) is an annual root crop which provides the major source of calories for over half a billion people around the world. Since its domestication ~10,000 years ago, cassava has been largely clonally propagated through stem cuttings. Minimal sexual recombination has led to an accumulation of deleterious mutations made evident by heavy inbreeding depression.MethodsTo locate and characterize these deleterious mutations, and to measure selection pressure across the cassava genome, we aligned 52 related Euphorbiaceae and other related species representing millions of years of evolution. With single base-pair resolution of genetic conservation, we used protein structure models, amino acid impact, and evolutionary conservation across the Euphorbiaceae to estimate evolutionary constraint. With known deleterious mutations, we aimed to improve genomic evaluations of plant performance through genomic prediction. We first tested this hypothesis through simulation utilizing multi-kernel GBLUP to predict simulated phenotypes across separate populations of cassava. ResultsSimulations showed a sizable increase of prediction accuracy when incorporating functional variants in the model when the trait was determined by

An understanding of student learning strategies is an important component of supporting academic success and avoiding difficulty. Prior inquiry has demonstrated certain learning strategies are more closely related to academic performance than others. The purpose of this study was to describe predictive relationships between the Metacognitive Awareness Inventory (MAI), Learning and Study Strategies Inventory (LASSI), and grade point average (GPA) in occupational therapy (OT) and physical therapy (PT) programs. A multi-center convenience sample of N=75(100%) entry-level students [OT: 34(45%); PT: 41(55%)] was included from Florida 32(42.7%), California 21(28%), and Texas 22(29.3%). A hierarchical linear regression analysis demonstrated the combination of predictors (MAI, Anxiety, Concentration, and Time Management [r=0.83; p

The isolation and characterization of neutralizing antibodies from infection and vaccine settings informs future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of great interest. Retroviral transduction to express Bcl-6 and Bcl-xL and transform primary B cells has been shown to promote long-term B cell survival and antibody secretion in vitro, and can be used to isolate antibodies from memory B cells. However, application of this methodology to B cell subsets from different tissues and B cells from chronically infected individuals has not been well characterized. Here, we characterize Bcl-6/Bcl-xL B cell immortalization across multiple tissue types and B cell subsets in healthy and HIV-1 infected individuals, as well as individuals recovering from malaria. In healthy individuals, naïve and memory B cell subsets from PBMCs and tonsil tissue transformed with similar efficiencies, and displayed similar characteristics with respect to their longevity and immunoglobulin secretion. In HIV-1-viremic individuals or in individuals with recent malaria infections, the exhausted CD27-CD21- memory B cells transformed with lower efficiency, but the transformed B cells expanded and secreted IgG with similar efficiency. Importantly, we show that this methodology can be used to isolate broadly neutralizing antibodies from HIV-infected individuals. Overall, we demonstrate that Bcl-6/Bcl-xL B cell immortalization can be used to isolate antibodies and generate B cell clones from different B cell populations, albeit with varying efficiencies.

Bioimaging enables the spatiotemporal visualization of biological processes at various scales empowered by a range of different imaging modalities and contrast agents. Upconversion nanoparticles (UCNPs) represent a distinct type of such contrast agents with the potential to transform bioimaging due to their unique optical properties and functional design flexibilities. This review explores and discusses the opportunities, challenges, and limitations that UCNPs exhibit as bioimaging probes and highlights applications with spatial dimensions ranging from the single nanoparticle level to cellular, tissue, and whole animal imaging. Recent advancements in bioimaging applications enabled by UCNPs, including super‐resolution techniques and multimodal imaging methods are summarized, and a perspective on the future potential of UCNP‐based technologies in bioimaging research and clinical translation is provided. This review may provide a valuable resource for researchers interested in exploring and applying UCNP‐based bioimaging technologies.

ABSTRACT Monkeypox, a zoonosis caused by the orthopox monkeypox virus (MPXV) that is endemic to Central and West Africa, was previously linked to sporadic outbreaks and rare, travel-associated cases. An outbreak of monkeypox in 2022 has spurred a public health emergency of international concern, and this outbreak is unprecedented in terms of its scale and epidemiology. The outbreak has been focused overwhelmingly in men who have sex with men; however, the trajectory of the outbreak remains uncertain, with spread now being reported in women and children. The mortality has been low (

Lewis acids have recently been shown to enable stereocontrol in photochemical cycloadditions, a difficult task due to the reactivity of excited-state compounds. Here the authors show that chiral Brønsted acids are competent chromophore activators in [2+2] cycloadditions, forming diastereomers disfavored in similar Lewis acid catalyzed photochemical reactions.

Background: Pediatric anxiety disorders are linked to dysfunction in multiple functional brain networks, as well as to alterations in the allocation of spatial attention. We used network-level analyses to characterize resting-state functional connectivity (rs-fc) alterations associated with 1) symptoms of anxiety and 2) alterations in stimulus-driven attention associated with pediatric anxiety disorders. We hypothesized that anxiety was related to altered connectivity of the frontoparietal, default mode, cingulo-opercular, and ventral attention networks and that anxiety-related connectivity alterations that include the ventral attention network would simultaneously be related to deviations in stimulus-driven attention. Methods: A sample of children (n = 61; mean = 10.6 years of age), approximately half of whom met criteria for a current anxiety disorder, completed a clinical assay, an attention task, and rs-fc magnetic resonance imaging scans. Network-level analyses examined whole-brain rs-fc patterns associated with clinician-rated anxiety and with involuntary capture of attention. Post hoc analyses controlled for comorbid symptoms. Results: Elevated clinician-rated anxiety was associated with altered connectivity within the cingulo-opercular network, as well as between the cingulo-opercular network and the ventral attention, default mode, and visual networks. Connectivity between the ventral attention and cingulo-opercular networks was associated with variation in both anxiety and stimulus-driven attention. Conclusions: Pediatric anxiety is related to aberrant connectivity patterns among several networks, most of which include the cingulo-opercular network. These results help clarify the within- and between-network interactions associated with pediatric anxiety and its association with altered attention, suggesting that specific network connections could be targeted to improve specific altered processes associated with anxiety.

Background: Behavioral activation is an evidence-based treatment for depression. Theoretical considerations suggest that treatment response depends on reinforcement learning mechanisms. However, which reinforcement learning mechanisms are engaged by and mediate the therapeutic effect of behavioral activation remains only partially understood, and there are no procedures to measure such mechanisms. Objective: To perform a pilot study to examine whether reinforcement learning processes measured through tasks or self-report are related to treatment response to behavioral activation. Method: The pilot study enrolled 13 outpatients (12 completers) with major depressive disorder, from July of 2018 through February of 2019, into a nine-week trial with BA. Psychiatric evaluations, decision-making tests and self-reported reward experience and anticipations were acquired before, during and after the treatment. Task and self-report data were analysed by using reinforcement-learning models. Inferred parameters were related to measures of depression severity through linear mixed effects models. Results: Treatment effects during different phases of the therapy were captured by specific decision-making processes in the task. During the weeks focusing on the active pursuit of reward, treatment effects were more pronounced amongst those individuals who showed an increase in Pavlovian appetitive influence. During the weeks focusing on the avoidance of punishments, treatment responses were more pronounced in those individuals who showed an increase in Pavlovian avoidance. Self-reported anticipation of reinforcement changed according to formal RL rules. Individual differences in the extent to which learning followed RL rules related to changes in anhedonia. Conclusions: In this pilot study both task- and self-report-derived measures of reinforcement learning captured individual differences in treatment response to behavioral activation. Appetitive and aversive Pavlovian reflexive processes appeared to be modulated by separate psychotherapeutic interventions, and the modulation strength covaried with response to specific interventions. Self-reported changes in reinforcement expectations are also related to treatment response. Trial Registry Name: Set Your Goal: Engaging in GO/No-Go Active Learning, #NCT03538535, http://www.clinicaltrials.gov.

Objective Digital monitoring technologies (e.g., smartphones and wearable devices) provide unprecedented opportunities to study potentially harmful behaviors such as suicide, violence, and alcohol/substance use in real‐time. The use of these new technologies has the potential to significantly advance the understanding, prediction, and prevention of these behaviors. However, such technologies also introduce myriad ethical and safety concerns, such as deciding when and how to intervene if a participant's responses indicate elevated risk during the study? Methods We used a modified Delphi process to develop a consensus among a diverse panel of experts on the ethical and safety practices for conducting digital monitoring studies with those at risk for suicide and related behaviors. Twenty‐four experts including scientists, clinicians, ethicists, legal experts, and those with lived experience provided input into an iterative, multi‐stage survey, and discussion process. Results Consensus was reached on multiple aspects of such studies, including: inclusion criteria, informed consent elements, technical and safety procedures, data review practices during the study, responding to various levels of participant risk in real‐time, and data and safety monitoring. Conclusions This consensus statement provides guidance for researchers, funding agencies, and institutional review boards regarding expert views on current best practices for conducting digital monitoring studies with those at risk for suicide—with relevance to the study of a range of other potentially harmful behaviors (e.g., alcohol/substance use and violence). This statement also highlights areas in which more data are needed before consensus can be reached regarding best ethical and safety practices for digital monitoring studies.

Background: As the number of total shoulder arthroplasties (TSAs) performed annually increases, some surgeons have begun to shift toward performing TSAs in the outpatient setting. However, it is imperative to establish the safety of outpatient TSA. The purpose of this systematic review was to define complication, readmission, and reoperation rates and patient-reported outcomes after outpatient TSA. Methods: A systematic review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using three databases (PubMed, Ovid, and Embase). English-language publications describing results on complication rates in patients who underwent TSA in an outpatient or ambulatory setting were included. All nonclinical and deidentified database studies were excluded. Bias assessment was conducted with the methodologic index for nonrandomized studies criteria. Results: Seven studies describing outcomes in outpatient TSA were identified for inclusion. The included studies used varying criteria for selecting patients for an outpatient procedure. The total outpatient 90-day complication rate (commonly including hematomas, wound issues, and nerve palsies) ranged from 7.1%-11.5%. Readmission rates ranged from 0%-3.7%, and emergency and urgent care visits ranged from 2.4%-16.1%. Patient-reported outcomes improved significantly after outpatient TSA in all studies. Two studies found a higher complication rate in the comparative inpatient cohort (P = .023-.027). Methodologic index for nonrandomized studies scores ranged from 9 to 11 (of 16) for noncomparative studies (n = 3), while all comparative studies received a score of a 16 (of 24). Conclusion: Outpatient TSA in properly selected patients results in a similar complication rate to inpatient TSA. Further studies are needed to aid in determining proper risk stratification to direct patients to inpatient or outpatient shoulder arthroplasty.

Bioinspired vascular networks transport heat and mass in multifunctional materials but lengthy multistep fabrication processes hinder large-scale application of structural vascular materials. Here, the authors report rapid, scalable, and synchronized fabrication of vascular thermosets and fiberreinforced composites under ambient conditions.

Objective Anterior cervical discectomy and fusion (ACDF) is the most common performed surgery in the cervical spine. Dysphagia is one of the most frequent complications following ACDF. Several studies have identified certain demographic and perioperative risk factors associated with increased dysphagia rates, but few have reported recent trends. Our study aims to report current trends and factors associated with the development of inpatient postoperative dysphagia after ACDF. Methods The National Inpatient Sample was evaluated from 2004 to 2014 and discharges with International Classification of Diseases procedure codes indicating ACDF were selected. Time trend series plots were created for the yearly treatment trends for each fusion level by dysphagia outcome. Separate univariable followed by multivariable logistic regression analyses were performed to evaluate predictors of dysphagia. Results A total of 1,212,475 ACDFs were identified in which 3.3% experienced postoperative dysphagia. A significant increase in annual dysphagia rates was observed from 2004–2014. Frailty, intraoperative neuromonitoring, 4 or more level fusions, African American race, fluid/electrolyte disorders, blood loss, and coagulopathy were all identified as significant independent risk factors for the development of postoperative dysphagia following ACDF. Conclusion Postoperative dysphagia is a well-known postsurgical complication associated with ACDF. Our cohort showed a significant increase in the annual dysphagia rates independent of levels fused. We identified several risk factors associated with the development of postoperative dysphagia after ACDF.

Objective Obesity has become a public health crisis and continues to be on the rise. An elevated body mass index has been linked to higher rates of spinal degenerative disease requiring surgical intervention. Limited studies exist that evaluate the effects of obesity on perioperative complications in patients undergoing anterior cervical discectomy and fusion (ACDF). Our study aims to determine the incidence of obesity in the ACDF population and the effects it may have on postoperative inpatient complications. Methods The National Inpatient Sample was evaluated from 2004 to 2014 and discharges with International Classification of Diseases procedure codes indicating ACDF were identified. This cohort was stratified into patients with diagnosis codes indicating obesity. Separate univariable followed by multivariable logistic regression analysis were performed for the likelihood of perioperative inpatient outcomes among the patients with obesity. Results From 2004 to 2014, estimated 1,212,475 ACDFs were identified in which 9.2% of the patients were obese. The incidence of obesity amongst ACDF patients has risen dramatically during those years from 5.8% to 13.4%. Obese ACDF patients had higher inpatient likelihood of dysphagia, neurological, respiratory, and hematologic complications as well as pulmonary emboli, and intraoperative durotomy. Conclusion Obesity is a well-established modifiable comorbidity that leads to increased perioperative complications in various surgical specialties. We present one of the largest retrospective analyses evaluating the effects of obesity on inpatient complications following ACDF. Our data suggest that the number of obese patients undergoing ACDF is steadily increasing and had a higher inpatient likelihood of developing perioperative complications.

Diffusion imaging aims to non-invasively characterize the anatomy and integrity of the brain's white matter fibers. We evaluated the accuracy and reliability of commonly used diffusion imaging methods as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927–1442 diffusion weighted images [DWIs] per individual). Diffusion imaging methods that allow for crossing fibers (FSL's BedpostX [BPX], DSI Studio's Constant Solid Angle Q-Ball Imaging [CSA-QBI], MRtrix3’s Constrained Spherical Deconvolution [CSD]) estimated excess fibers when insufficient data were present and/or when the data did not match the model priors. To reduce such overfitting, we developed a novel Bayesian Multi-tensor Model-selection (BaMM) method and applied it to the popular ball-and-stick model used in BedpostX within the FSL software package. BaMM was robust to overfitting and showed high reliability and the relatively best crossing-fiber accuracy with increasing amounts of diffusion data. Thus, sufficient data and an overfitting resistant analysis method enhance precision diffusion imaging. For potential clinical applications of diffusion imaging, such as neurosurgical planning and deep brain stimulation (DBS), the quantities of data required to achieve diffusion imaging reliability are lower than those needed for functional MRI.

Recent advances in wireless data transmission technology have the potential to revolutionize clinical neuroscience. Today sensing-capable electrical stimulators, known as “bidirectional devices”, are used to acquire chronic brain activity from humans in natural environments. However, with wireless transmission come potential failures in data transmission, and not all available devices correctly account for missing data or provide precise timing for when data losses occur. Our inability to precisely reconstruct time-domain neural signals makes it difficult to apply subsequent neural signal processing techniques and analyses. Here, our goal was to accurately reconstruct time-domain neural signals impacted by data loss during wireless transmission. Towards this end, we developed a method termed Periodic Estimation of Lost Packets (PELP). PELP leverages the highly periodic nature of stimulation artifacts to precisely determine when data losses occur. Using simulated stimulation waveforms added to human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Then, we applied PELP to local field potential (LFP) recordings collected using an implantable, bidirectional DBS platform operating at various telemetry bandwidths. By effectively accounting for the timing of missing data, PELP enables the analysis of neural time series data collected via wireless transmission—a prerequisite for better understanding the brain-behavior relationships underlying neurological and psychiatric disorders.

Background: Recent findings indicate that ghrelin, particularly the unacylated form (UnAG), acutely stimulates skeletal muscle fatty acid oxidation (FAO) and can preserve insulin signaling and insulin-stimulated glucose uptake in the presence of high concentrations of saturated fatty acids. However, we recently reported that the stimulatory effect of ghrelin on FAO and subsequent ability to protect insulin stimulated glucose uptake was lost following 6-weeks (6w) of chronic high fat feeding. In the current study we examined the effects of both short-term 5 day (5d) and chronic 6w high-fat diet (HFD) on muscle ghrelin response, and whether exercise training could prevent the development of muscle ghrelin resistance with 6w of HFD Methods and Results: Soleus muscle strips were isolated from male rats to determine the direct effects of acylated (AG) and UnAG isoforms on FAO and glucose uptake. A 5d HFD did not alter the response of soleus muscle to AG or UnAG. Conversely, 6w of HFD was associated with a loss of ghrelin's ability to stimulate FAO and protect insulin stimulated glucose uptake. Muscle response to UnAG remained intact following the 6w HFD with chronic exercise training. Unexpectedly, muscle response to both AG and UnAG was also lost after 6w of low-fat diet (LFD) consumption. Protein content of the classic ghrelin receptor, GHS-R1a, was not affected by diet or training. Corticotropin-releasing hormone receptor-2 (CRF-2R) content, a putative receptor for ghrelin in muscle, was significantly decreased in soleus from 6w HFD-fed animals and increased following exercise training. This may explain the protection of UnAG response with training in HFD-fed rats but does not explain why ghrelin response was also lost in LFD-fed animals. Conclusions: UnAG protects muscle glucose uptake during acute lipid oversupply, likely due to its ability to stimulate FAO. This effect is lost in 6w HFD-fed animals but protected with exercise training. Unexpectedly, ghrelin response was lost in 6w LFD-fed animals. The loss of ghrelin response in muscle with a LFD cannot be explained by a change in putative ghrelin receptor content. We believe that the sedentary nature of the animals is a major factor in the development of muscle ghrelin resistance and warrants further research.

Trans-ethnic genetic correlation is significantly less than 1 for many diseases. Here, the authors stratify this correlation by genomic annotations, finding that loci whose causal disease effect sizes differ between ethnicities are likely impacted by selection, particularly positive selection.

Ghrelin is released from the stomach as an anticipatory signal prior to a meal and decreases immediately after. Previous research has shown that both acylated (AG) and unacylated (UnAG) ghrelin blunt adrenoreceptor-stimulated lipolysis in rat white adipose tissue (WAT) ex vivo. We investigated whether acute or chronic consumption of a high fat diet (HFD) impaired the ability of ghrelin to regulate adipose tissue lipolysis, and if this impairment could be restored with exercise. After 5 days (5d) of a HFD, or 6 weeks (6 w) of a HFD (60% kcal from fat) with or without exercise training, inguinal and retroperitoneal WAT was collected from anesthetized rats for adipose tissue organ culture. Samples were treated with 1 μM CL 316,243 (CL; lipolytic control), 1 μM CL+150 ng/ml AG or 1 μM CL+150 ng/ml UnAG. Incubation media and tissue were collected after 2 hours. Colorometric assays were used to determine glycerol and free fatty acid (FFA) concentrations in media. Western blots were used to quantify the protein content of lipolytic enzymes and ghrelin receptors in both depots. CL stimulated lipolysis was evidenced by increases in glycerol (p

We describe the case of a 57-year-old female who underwent bilateral ceramic-on-polyethylene total hip arthroplasties performed in 2015. She presented to us in 2018 with headaches, fatigue, and right hip pain 5 months after an atraumatic right polyethylene liner failure for which she did not seek treatment. She was found to have imaging consistent with an adverse local tissue reaction and massive pseudotumor formation. During revision surgery, fracture of the acetabular liner was noted, with ceramic head wear through the titanium cup. In the months after her debridement and prosthesis revision, the patient continued to complain of systemic symptoms including weakness, fatigue, headaches, and vision problems. Serum titanium levels were found to be 100 times higher than normal. This case serves as a rarely reported example of titanium toxicity and titanium pseudotumor formation in the setting of polyethylene failure.

The foundation of wisdom is rooted in experience, and thus we reflexively call upon our senior leaders, mentors, coaches, and family members for guidance in our personal and professional lives. Witnessing the weathered perspectives of others allows for an internal audit of one’s own strengths and deficiencies, which ultimately inspires personal growth. This experience is heightened when both the mentor and the mentee, for example, share a common goal. The field of congenital interventional cardiology, with its constant evolution and diverse technical approaches, requires a lifetime of learning, as well as safe passage of knowledge to the next generation. While there are published recommendations for what to consider when completing this task, hearing the sentiments of those with experience may be more profitable for future fellows and current interventionalists. In part one of a series, we hope to accomplish this goal by presenting an opportunity to learn from our experienced colleagues on the topic of congenital interventional cardiology training. Specifically, we aim to share expert opinions on how to succeed as a congenital interventional fellow, illustrate the diversity of teaching styles and expectations in various healthcare systems, and for the mid-career interventionalists, provide insight into the character traits of a successful mentor of interventional fellows.